ArticleAmerican journal of human genetics2019
Extreme Polygenicity of Complex Traits Is Explained by Negative Selection.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Empirically determined baseline masking strategies and other considerations for gene-level burden tests.Nature genetics · 2026Pooled it
- Neuropsychiatry genetics in Africa.Nature communications · 2026Review
- A heritability-optimized method for functional prioritization of rare coding variants in complex traits.Nature genetics · 2026Article
- Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Correlations between causal effect sizes of proximal SNPs vary with functional annotations and implicate stabilizing selection.Nature genetics · 2026Article
- Distinguishing different psychiatric disorders using DDx-PRS.Nature genetics · 2026Article
- Article
- Determinants of functional burden pleiotropy and gene dosage responses across human traits.Nature communications · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
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- Genetic pathways linking oxytocin-vasotocin hypothalamic subunit architecture with psychiatric and metabolic traits.Molecular psychiatry · 2026Article
- An empirical Bayes framework for burden and dispersion association tests helps prioritize rare variants associated with Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- A Multi-Context Regulome-Wide Association Atlas for Genetic Studies of Aging Brain Disorders.medRxiv : the preprint server for health sciences · 2026Article
- Meta-ERS: an exposome-based risk score using non-genetic factors to guide osteoporosis prevention.Journal of translational medicine · 2026Article
- Principled measures and estimates of trait polygenicity.American journal of human genetics · 2026Article
- Unravelling the genetic architecture of cerebral small vessel disease in the context of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Article
- NATURAL VARIATION IN RADIOTOLERANCE IS ASSOCIATED WITH DIFFERENCES IN INNATE IMMUNE ACTIVITY AND S-PHASE TRANSCRIPTION IN DROSOPHILA MELANOGASTER.bioRxiv : the preprint server for biology · 2026Article
122 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Complex traits and common diseases are extremely polygenic, their heritability spread across thousands of loci. One possible explanation is that thousands of genes and loci have similarly important biological effects when mutated. However, we hypothesize that for most complex traits, relatively few genes and loci are critical, and negative selection-purging large-effect mutations in these regions-leaves behind common-variant associations in thousands of less critical regions instead. We refer to this phenomenon as flattening. To quantify its effects, we introduce a mathematical definition of polygenicity, the effective number of independently associated SNPs (M
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